Inactivated virus vaccines have the advantage that they do not comprise live infective viral material obviating the possibility of reversion of the viruses to a virulent state.
However, inactivated virus vaccines and subunit vaccines require the production of large quantities of the active vaccine component and are expensive to produce. Furthermore, these types of vaccines also require several inoculations with the vaccine in the presence of an adjuvant in order to provide immunity which is effective and long lasting.
MLV vaccines have important advantages in that they induce a rapid and long lasting immune response, both humoral and cellular, without the need of large quantities of the active component in the absence of adjuvants.
However, these vaccines still bear the risk of the vaccine virus being shed into the environment by the vaccinated animal, in particular when the live vaccine is administered via the natural route, e.g. intranasally.
Although MLV vaccines have been proven to be safe and efficacious there is a risk that the vaccine viruses revert to a more virulent state, or that the MLV spreads to other animals which are more susceptible for the MVL vaccine virus.
In particular, for the purpose of risk assessment by regulatory authorities with respect to vaccines based on genetically modified organisms, especially live organisms expressing foreign genes, the aspect of possible shedding of these organisms in the environment is very important.
Thus, it can be appreciated that herpesvirus vaccines which display the advantages of live virus inoculation but which are confined to the vaccinated animals are highly desirable.
The envelope glycoproteins of herpesviruses are major targets of the immune response to herpes vital infection. Furthermore, these glycoproteins are important for the interaction of the virus with its host cell.
The pseudorabies virus (PRV) is a herpesvirus that causes an economically significant disease in swine called Aujeszky's disease. It has been well documented that the glycoprotein D (gD) homolog of PRV (glycoprotein 50, gp50) is a major immunogen of PRV which is the most potent for the induction of protective immunity in an infected host animal (Eloit, M. et al., Archs. Virol. 99, 45-56, 1988; Marchioli, C. et al., Am. J. Vet.res. 49, 860-864, 1988; Ishii, H. et al., J. Gen. Virol. 69, 1411-1414, 1988; Marchioli, C. C. et al., J. Virol. 61, 3977-3982, 1987; Wathen, M. W. et al., J. Virol. 51, 57-62, 1984, Mettenleiter, T. C., Comp. Immun. Microbiol. Infect. Dis. 14, 151-163, 1991).
Furthermore, Rauh, I. and Mettenleiter, T. C. (J. Virol. 65, 5348-5356, 1991), and Peeters, B. et al., (J. Virol. 66, 894-905, 1992) constructed a gp50-negative (gp50-) PRV mutant which is phenotypically gp50-positive as result of their growth in a cell line expressing gp50. It was concluded therein that for the in vitro replication of the virus gp50 is essential for penetration into a cell and is not required for cell-cell spread of the virus.